Continuous repetitions of a cell cycle maintain various functions of tissues while balancing the death and proliferation of cells. When the balance is broken, a disease is caused. In normal cell tissue, the number of tissue cells is regularly maintained due to the balance of the proliferation and death of cells. On the other hand, in tumorous cell tissue, since cell death is not properly carried out compared to rapid cell proliferation, the number of cells is greatly increased unlike the normal tissue and the cells become cancer cells (Raff. M. C., Nature, 356:397, 1992). Cell death is very important in the maintaining of such balance, and has two types of mechanisms. One is known as a conventional type of necrosis which is generally passively and accidentally caused. Morphologically, necrosis is characterized by causing a swelling of mitochondria and protoplasm, and nucleus damage, and then cells are led to death due to cytolysis and autolysis. For example, tissue necrosis is generally caused by physical injury or chemical toxicity of a cell. The other is apoptosis which is programmed cell death. Apoptosis is one type of cell death occurring in physiological and clinical conditions, and is closely related to a fetal development process, a tissue's growth, differentiation and homeostasis, and a cell's differentiation, growth, and maturation.
Sphingolipid is one type of membrane lipid which very importantly acts on the structural formation of a lipid bilayer. For the last 20 to 30 years, molecular-biological or biochemical researches on functions of sphingolipid and sphingolipid metabolite have been continued up to now. For such functions, researches on immunological or cell-biological functions through cell proliferation, apoptosis, cell migration, senescence have been conducted so far. However, specific results have been not yet achieved.
Skin is an organ which is positioned in the outermost layer of a human body, and is always exposed to an outer stimulus. Proliferative skin diseases are spread through the world, and millions of people and domesticated animals suffer from the diseases. The proliferative skin diseases are characterized by causing proliferation or differentiation of keratinocytes, and also may relate to imperfect epidermal differentiation. Psoriasis is the most serious disease in proliferative skin diseases related to the present invention.
Psoriasis is a hyper-proliferative skin disease of human skin, which is generally characterized by causing a macule covered with thickened squama (layered lump of keratin). Psoriasis is a representative intractable skin disease that is hardly completely healed, and its relapse and relief are repeated at intervals (Korean Dermatological Association, textbook compilation committee, 4th revised edition, dermatology, Ch 12, papulosquamous disease, p 221, 2001). It is known that about 3% of Caucasians, about 2% of Native Americans, and about 1% of African-Americans suffer from psoriasis. Psoriasis is caused by hyper-proliferation of keratinocytes. Cells in normal skin reach a granulosa from a basal layer within about 4 weeks while cells with psoriasis rapidly proliferate and then reach the granulosa within only 6 to 9 days (Grove, G. L., Int. J. Dermatol., 18, 111-122, 1979). As described above, abnormal proliferation of cells is a cause of psoriasis, and thus the present treatment focuses on a delay of skin cell proliferation and a reduction of inflammation. Topical treatments for psoriasis may comprise a steroid cream treatment, an ultraviolet ray treatment (UVB, 290-320 nm), and a treatment using a vitamin D ointment for inhibiting the proliferation of skin cells. A steroid ointment is very effective but its therapeutic effect is not maintained for a long time. Thus, over the course of the application of a steroid ointment, its effect is reduced and side effects such as skin atrophy are caused. The ultraviolet ray treatment has a therapeutic effect which is maintained for a relatively long time, but causes troubles such as periodical hospital visits for treatments. Meanwhile, when the ultraviolet ray treatment is administered over too long a period of time, it may promote photoaging and increase the possibility of skin cancer. The vitamin D ointment does not cause the same side effects as the steroid ointment, but is effective in only 50% of patients treated by the steroid ointment. Further, it is known that the vitamin D ointment is very acrid. Psoriasis not only promotes angiogenesis but also rapidly proliferates keratinocytes. Accordingly, there have been suggested medicines for inducing apoptosis of such keratinocytes as effective therapeutic agents.
Malignant melanoma is the most dangerous cancer among various skin cancers, and is formed in a similar shape to a spot on a sole. In general, in frequent cases, people let the malignant melanoma go untreated without recognizing it as cancer, and in the end, they lose their lives. Among various skin cancers, a conspicuous symptom indicates that a cancer has already considerably progressed, and thus it is likely that the cancer spreads to other organs. However, metastasis of the malignant melanoma very strongly occurs, compared to those in other cancers. Thus, in many cases, people lose their lives by metastasized melanoma, not by malignant melanoma occurring in skin. Also, a cancer occurring in the skin has a considerably wide range, and thus a considerably wide area for an operation or a treatment is appointed so that the corresponding cancer region and its circumference can be scraped out or cut out. For this reason, patients may refuse treatment while seriously worsening a disease state. This repeatedly causes a vicious cycle. Besides these characteristics of the cancer, there are problems in that in general, people do not consider skin cancer as a serious disease, and let the disease go untreated, and many patients even refuse treatment. From 1980 to 2004, malignant melanoma incidences among young Caucasian women have risen by 50% per year. Also, the plastic surgery team of a national medical center carried out a retrospective analysis on 251 operation cases of skin cancer over 15 years from 1993 to 2007. As a result, in 50% of the cases, skin-cancer relapse patients secondarily relapsed into cancer again.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.